Age-Modulated Associations between KIBRA, Brain Volume, and Verbal Memory among Healthy Older Adults
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The resource modulation hypothesis suggests that the influence of genes on cognitive functioning increases with age. The KIBRA single nucleotide polymorphism rs17070145, associated with episodic memory and working memory, has been suggested to follow such a pattern, but few studies have tested this assertion directly. The present study investigated the relationship between KIBRA alleles (T carriers vs. CC homozygotes), cognitive performance, and brain volumes in three groups of cognitively healthy adults —middle aged (ages 52 - 64, n = 38), young old (ages 65 - 72, n = 45), and older old (ages 73 - 92, n = 62) – who were carefully matched on potentially confounding variables including apolipoprotein ε4 status and hypertension. Consistent with our prediction, T carriers maintained verbal memory performance with increasing age while CC homozygotes declined. Voxel-based morphometric analysis of magnetic resonance images showed an advantage for T carriers in frontal white matter volume that increased with age. Focusing on the older old group, this advantage for T carriers was also evident in left lingual gyrus gray matter and several additional frontal white matter regions. Contrary to expectations, neither KIBRA nor the interaction between KIBRA and age predicted hippocampal volumes. None of the brain regions investigated showed a CC homozygote advantage. Taken together, these data suggest that KIBRA results in decreased verbal memory performance and lower brain volumes in CC homozygotes compared to T carriers, particularly among the oldest old, consistent with the resource modulation hypothesis.
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KIBRA allelic variants are associated with enhanced episodic memory performance in adults, particularly regarding the maintenance of memory during aging.
“KIBRA, whose allelic variants have been associated with enhanced episodic memory performance in adults, particularly regarding the maintenance of memory during aging (Stickel et al. 2018)”
From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Stickel et al. 2018
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Hayek, D., Antonenko, D., Witte, A. V., Lehnerer, S., Meinzer, M., Külzow, N., Prehn, K., Rujescu, D., Schneider, A., Grittner, U., et al. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.113081 · Cited by 15 · see citing works
The Hippo signaling pathway as a therapeutic target in Alzheimer’s disease
Chen, D., Wigglesworth-Littlewood, S., & Gunn‐Moore, F. J. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00891-4 · Cited by 10 · see citing works
KIBRA Gene Variant Is Associated with Ability in Chess and Science
Ahmetov, I. I., Валерьевна, В. Е., Yerdenova, M. B., Datkhabayeva, G. K., Bouzid, A., Bhamidimarri, P. M., Sharafetdinova, L. M., Egorova, E. S., Semenova, E. A., Gabdrakhmanova, L. J., et al. (2023) · Genes · doi:10.3390/genes14010204 · Cited by 10 · see citing works
Wang, J., Wu, S., Sun, Y., Lu, J., Zhang, J., Fang, Y., Zhao, Q., Liang, X., Zhang, W., Chen, Q., et al. (2022) · Brain Imaging and Behavior · doi:10.1007/s11682-022-00703-z · Cited by 6 · see citing works
Stickel, A. M., McKinnon, A. C., Matijevic, S., Grilli, M. D., Ruiz, J. M., & Ryan, L. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.627322 · Cited by 5 · see citing works
Self-citationKIBRA-PKCγ signaling pathway modulates memory performance in mice and humansPreprint
Tian, M., Chen, Q., Graves, A. R., Goldschmidt, H. L., Johnson, R. C., Weinberger, D. R., & Huganir, R. L. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.26.465926 · Cited by 5 · see citing works
Homayouni, R., Daugherty, A. M., Yu, Q., Raz, N., & Ofen, N. (2023) · Brain Structure and Function · doi:10.1007/s00429-023-02716-w · Cited by 4 · see citing works
del Ángel, M., Tsutiya, A., Hayani, H., Madencioglu, D., Kul, E., Caliskan, G., Demiray, Y. E., Dityatev, A., & Stork, O. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70094 · Cited by 1 · see citing works
“Further upstream, another regulator of the Hippo pathway that is highly enriched in the brain is KIBRA, whose allelic variants have been associated with enhanced episodic memory performance in adults, particularly regarding the maintenance of memory during aging (Stickel et al. 2018).”
From Synapses to Circuits, the Role of KIBRA and the WWC Family in Adaptive Brain Function
Volk, L. J. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70514 · Cited by 1 · see citing works
Association Between Genetically Predicted Memory and Self-Reported Foreign Language Proficiency
Yerdenova, M. B., Datkhabayeva, G. K., Zholdassova, M., Kamzanova, A. T., Sadvakassova, Z., Bouzid, A., Bhamidimarri, P. M., Hamoudi, R., Semenova, E. A., Larin, A. K., et al. (2025) · Genes · doi:10.3390/genes16050589 · Cited by 1 · see citing works
The dynamic characteristic and mental mechanism of retrospective duration estimation
Lianlian, Y. A. N. G., Huang, X., Liu, P., & Yue, T. (2019) · Advances in Psychological Science · doi:10.3724/sp.j.1042.2019.00221
The Genetics of Cognitive Abilities
Papenberg, G., & Bäckman, L. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108552684.034
An online, updated battery for episodic memory and executive control composites in older adults
Jensen, A., Carton, S., Ardilliez, O., Hu, R., & Davidson, P. S. R. (2025) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2025.2544730
Introduction to age-related cognitive-behavioural changes
Broderick, M.-Z. L., Taji, H., Hajj, F., Balakumar, B., Al-Achkar, O., & Tasnim, D. (2025) · Progress in brain research · doi:10.1016/bs.pbr.2025.08.019
- Authors
- Stickel, A., Kawa, K., Walther, K., Glisky, E., Richholt, R., Huentelman, M., & Ryan, L.
- Affiliations
- University of Arizona (US)
- Universitätsklinikum Erlangen (DE)
- Translational Genomics Research Institute (US)
- Corresponding author
- Ryan, Lee
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-01-10
- Volume
- 9
- Pages
- 431-431
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC5767716
- OpenAlex
- W2783955096
- Cited by
- 16
- References
- 85
- Citations by year
- 2026: 1 · 2025: 5 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UA Campus Repository (The University of Arizona) (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Evelyn F. McKnight Brain Research Foundation
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- KIBRA, verbal memory, brain volume, white matter, gray matter, hippocampus, aging, older adults, genetic polymorphism, cognitive aging, frontal lobe
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